RhoGAP domain-containing fusions and PPAPDC1A fusions are recurrent and prognostic in diffuse gastric canceropen access
- Authors
- Yang, Hanna; Hong, Dongwan; Cho, Soo Young; Park, Young Soo; Ko, Woo Ri; Kim, Ju Hee; Hur, Hoon; Lee, Jongkeun; Kim, Su-Jin; Kwon, Sun Young; Lee, Jae-Hyuk; Park, Do Youn; Song, Kyu Sang; Chang, Heekyung; Ryu, Min-Hee; Cho, Kye Soo; Kang, Jeong Won; Kook, Myeong-Cherl; Thiessen, Nina; He, An; Mungall, Andy; Han, Sang-Uk; Kim, Hark Kyun
- Issue Date
- Dec-2018
- Publisher
- Nature Publishing Group
- Citation
- Nature Communications, v.9, no.1, pp 1 - 13
- Pages
- 13
- Indexed
- SCI
SCIE
SCOPUS
- Journal Title
- Nature Communications
- Volume
- 9
- Number
- 1
- Start Page
- 1
- End Page
- 13
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/114380
- DOI
- 10.1038/s41467-018-06747-4
- ISSN
- 2041-1723
2041-1723
- Abstract
- We conducted an RNA sequencing study to identify novel gene fusions in 80 discovery dataset tumors collected from young patients with diffuse gastric cancer (DGC). Twenty-five in-frame fusions are associated with DGC, three of which (CLDN18-ARHGAP26, CTNND1-ARHGAP26, and ANXA2-MYO9A) are recurrent in 384 DGCs based on RT-PCR. All three fusions contain a RhoGAP domain in their 3’ partner genes. Patients with one of these three fusions have a significantly worse prognosis than those without. Ectopic expression of CLDN18-ARHGAP26 promotes the migration and invasion capacities of DGC cells. Parallel targeted RNA sequencing analysis additionally identifies TACC2-PPAPDC1A as a recurrent and poor prognostic in-frame fusion. Overall, PPAPDC1A fusions and in-frame fusions containing a RhoGAP domain clearly define the aggressive subset (7.5%) of DGCs, and their prognostic impact is greater than, and independent of, chromosomal instability and CDH1 mutations. Our study may provide novel genomic insights guiding future strategies for managing DGCs. © 2018, The Author(s).
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